Composition and Method for Using Medicament for Endodontic Irrigation, Stem Cell Preparation and Tissue Regeneration

ABSTRACT

A composition for tissue degradation and removal and disinfection is provided for dental and medical applications. It can function as a single intra-canal irrigant that eradicates microorganisms as it facilitates the debridement of a root canal system. It contains one or more hydoxides, a thioglycolate compound, sodium hypochlorite, sodium chloride, sodium chlorate, oxygen, and water, such as lime water and purified water, The thioglycolate compound is capable of degrading a cell by disrupting disulfide bonds in its proteins. The sodium hypochlorite enhances its function. The composition may also incorporate mineral oil, urea, cetearyl alcohol, D&amp;C yellow No. 8, chromium hydroxide, theobroma cocoa seed butter, iron oxides, fragrances, lanolin, and/or ceteareth-20. It is effective against  Enterococcus faecalis.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. patent applicationSer. No. 14/592,148 filed Jan. 8, 2015 which is a continuation of U.S.patent application Ser. No. 14/331,813 filed Jul. 15, 2014 which is acontinuation-in-part of co-pending U.S. patent application Ser. No.13/954,434 filed Jul. 30, 2613, entitled “COMPOSITION AND METHOD OFUSING MEDICAMENT FOR ENDODONTIC IRRIGATION, STEM CELL PREPARATIONS ANDTISSUE REGENERATION” which claims the benefit of U.S. ProvisionalApplication Ser. No. 61/717,691, filed Oct. 24, 2012, entitled“COMPOSITION AND METHOD OF USING MEDICAMENT FOR ENDODONTIC IRRIGATION,STEM CELL PREPARATIONS AND TISSUE REGENERATION.” All of the foregoingare incorporated herein by reference in their entirety.

BACKGROUND 1. Field of the Invention

The present invention provides a novel composition and a novel methodfor irrigating unprepared and prepared surfaces for dental and medicalprocedures and, in particular, for an intra-canal medicament forendodontic irrigation, stem cell preparations, tissue regeneration,removal of smear layer, disinfection and removing pulpal tissue. Thepresent invention provides a novel single medicament that is abactericidal agent effective against microorganisms such as Enterococcusfaecalis, Streptococcus rnutans and Candida albicans.

2. Description of the Related Art

Root canal treatment is required when tissues in root canals areinjured, infected, inflamed irreversibly (pulpits), has abnormal growth,or is needed for restorative treatment. Bacteria destroys pulp (i.e.,soft tissues occupying inner space of teeth) causing pulpal necrosis,inflammation (pulpitis), and internal granulomas or closed chronicgranulomas pulpitis (i.e., abnormal growth of tissues due to bacteriaand inflammation).

Pulpal inflammation including inflammation caused by microorganisms suchas bacteria and fungi requires root canal therapy to eliminate thesemicroorganisms. The root canal treatment is performed in order to removebacteria, debris, tissues, calcifications, and organic matter from theroot canal and then filling the space in order to prevent bacterialinvasion and irritation into surrounding tissues. A failed root canaltreatment is caused by the microorganisms that contaminate a root canalsystem when the microorganisms leak out from the root canal intosurrounding bones which is called an apical periodontitis (i.e., apicalinflammation around root apex). Typically, the dominant microorganismpresent in the apical periodontitis is Enterococcus faelcalis and isalso one of the most commonly isolated bacteria in root canalinfections.

The success of root canal (or endodontic) therapy is dependent on theremoval of all tissues, debris and microorganisms from the root canalarea. Treatment complication or failures may occur if pulpal tissue,infecting bacteria, and microorganisms are not eliminated completelyfrom the root canal space and/or the dentinal tubules. Bacterialinvasion of microscopic spaces in dentin, irregularities orimperfections in the dentin structure including isthmuses,ramifications, accessory canals, complex root canal systems and apicaldeltas, can further complicate the root canal treatment and its outcome.Pulpal calcifications, pulp stones, and calcified canals may prevent apractitioner from removing all the pulpal tissue in the root canal spaceaffecting the success of the root canal treatment. Also, biofilms (i.e.,layers of microorganisms, proteins, and polysaccharides) and a smearlayer (debris from mechanical preparations) needs to be removed with allof its microorganisms eradicated. Root canal treatment is indicated toremove abnormal growth of pulpal tissue of pulp polyps (chronichyperplastic pulpitis) and of granulomatous tissue of internalresorption caused by bacteria and inflammation.

Bacteremias, caused from the presence of bacteria in the blood afterdental procedures, are a major concern to the American DentalAssociation (ADA), and the American Association of Orthopedic Surgeons(AAOS). The bacteria that are prevalent in endodontic infections mayalso cause bone infections, and both the ADA and the AAOS recommendprophylactic antibiotics to be given to patients in certain cases (e.g.total hip replacement) to prevent bacteremia and infection followingdenial procedures. Presently, the guidelines have changed and therefore,an orthopedic implant does not routinely require pre-medication.However, the guidelines do recommend that each patient should beevaluated based on the need for prophylactic antibiotics on a case bycase basis by their dental and medical professionals.

The bacteria, Streptococcus mutans and Enterococcus faelcalis, which areprevalent in endodontic infections, are also prevalent in infections inthe bones. The fungus Candida has also been found in the infections inthe bones. In addition, Streptococcus mutans is one of the leadingcauses of infective endocarditis. Therefore, both the ADA and theAmerican Heart Association (AHA) recommend antibiotic prophylaxis forthose dental patients that may be at a risk for developing an infectionwhen the Streptococcus mutans enters their blood streams following thedental procedures and causes bacteremia. There is a documented case in‘Heart Lung’ publication on May 7, 1988, of streptococcus mutans thatcauses a hematagenous bone infection in lumbar vertebrae. Therefore, itis important to eradicate bacteria and fungi from the pulpal cavity toaid in preventing the formation of bacteremia after the dentalprocedures. Further, it is important to eradicate these microorganismsnot only from the tooth but also from within a bony cavity or from anorthopedic prosthesis for maintaining the health of the patient.However, currently, there is no single medicament or irrigant that isbactericidal against Streptococcus mutans, Enterococcus faelcalis, andCandida.

Currently, the practitioner uses many types of irrigants in order tochemo-mechanically prepare the root canal system for obturation andregeneration of the tissues. The present endodontic treatments requireuse of a combination of medicaments and irrigants for thechemo-mechanical instrumentation, cleansing, disinfection, and preparinga site for endodontic regeneration. Some endodontic irrigants areutilized for their tissue dissolving ability. For example, sodiumhypochlorite is a widely used tissue dissolving agent. Sodiumhypochlorite's effectiveness is dependent on its concentration andirrigation time and is highly effective at 525% for 40 minutes andineffective at 1.3-2.5%. However, Sodium hypochlorite tends to softenthe dentin which is a contraindication for its prolonged use. Further,antibacterial agents are either bactericidal or bacteriostatic. Forexample, chlorohexidine is bactericidal while a mixture of tetracycline,an acid, and a detergent (MTAD) is bacteriostatic. Furthermore, otherendodontic irrigants are chelating agents likeEthylenediaminetetraacetic acid (EDTA) that remove the smear layer anddecalcify dentin. In endodontic regeneration, Triple Antibiotic Paste(TAP), a combination of metronidazole, ciprofloxacin, and rninocycline,is used for intracanal disinfection which is effective at a highconcentration but causes discoloration. Also, Double Antibiotic Paste(DAP), a mixture of metronidazole and ciprofloxin, is used during theendodontic regeneration due to, its antibacterial properties but it alsocauses discoloration. Further, calcium hydroxide paste is used for itsalkaline property but is ineffective in eradicating endodonticpathogens. As discussed above, the success of the root canal treatmentis dependent on removing all the contents from within the root canalsystem before obturation. As the American Association of Endodontists(AAE) stated in 2011, in “Endodontics: Colleagues for Excellence”, “thesearch for an ideal material and/or technique to completely cleaninfected root canals continues”.

Pulp calcifications within the root canal systems are obstructions todebridement in a variety of forms. Pulp stones are isolated areas ofcalcifications. While other calcifications take the form of diffusecalcification and irregular linear calcifications. Calcifications andcalcification blockages present a problem for the practitioner in orderto successfully negotiate the canal during instrumentation. Pulpalcalcifications prevent root canals to be accessed and located. Pulpalcalcifications can block the canal and prevent complete instrumentationof the canal space.

Conventional endodontic, intra-canal medicaments have specificlimitations. For example, sodium hypochlorite and calcium hydroxide donot have the ability to eradicate all the bacteria in the root canalsystem. Sodium hypochlorite and calcium hydroxide need to be in directcontact for it to be effective but this is difficult to attain. Thedirect contact cannot be gained when there are calcifications presentthat are natural obstructions. Also, when chlorohexidine is mixed withsodium hypochlorite during the instrumentation, an orange-brownprecipitate is formed that is hard to remove and can stain.

As another example, sodium hypochlorite can dissolve organic tissue bydisrupting the cell's metabolism and its ability to function, but cannotpredictably inactivate endotoxins. Also, sodium hypochlorite loses itseffectiveness when it is diluted. Furthermore, it is irritating totissues. Sodium hypochlorite is not effective against bacteria such asenterococcus faecalis in the biofilms. Calcium hydroxide, an intra-canalmedicament, has some antibacterial effect but is ineffective against theenterococcus faecalis, which is the most commonly isolated microorganismfound in periapical lesions of the failed root canal treatmentprocedures.

Additionally, ethylenediaminetetraacetic acid (EDTA) which is watersoluble is effective for removing inorganic material as a chelatingagent but not as an effective antibacterial agent. However, EDTA shouldnot be used with sodium hypochlorite, as it reduces the availablechloride making sodium hypochlorite not effective as an irrigant.

MTAD is a mixture of doxycycline, citric acid, and Tween 80 (adetergent) in order to remove some, of the smear layer. However, it isnot effective against fungi within the root canal system. Also, it canhave a negative effect on the bond strength of root canal sealers whenused as a final intra-canal rinse. Additionally, chlorohexidine orclorohexidine digluconate that are both water soluble can be used fordisinfection but cannot dissolve tissue.

Pulp tissues contain disulfide bonds that are derived by coupling of twothiol groups, The linkage is called as an SS bond or disulfide bridge.When the disulfide bonds are broken, cell death or apoptosis occurs.Apoptosis is needed to eradicate bacteria from the root canal during thechemo-mechanical instrumentation and to prevent bacteria fromre-infecting the root canal and causing apical periodontitis. Disulfidebonds are present in bacteria as they serve as a protective role forbacteria. Further, in humans also, disulfide bonds are found insecretory proteins, lysosomal proteins, mRNA, red blood cells, whiteblood cells, hematopoeisis cells, fibronectin, blood vessels,immunoglobins macrophages, neutrophils, membrane proteins, antibodies,and exoplasmic domains of membrane proteins in endoplasmic reticulum.Further, disulfide bonds are also found in nuerokeratin of themyelinated sensory nerve A fibers that can be found in the pulpaltissue. Disulfide bonds are needed for protein folding. Disulfide bondformation takes place in the endoplasmic reticulum. The soft tissue ofthe bony cavity contain hematopoesis cells, red blood cells, white bloodcells, and blood vessels which contain disulfide bonds.

Traditionally, the dental professional or practitioner prepares a rootcanal system by chemo-mechanically debriding the tissue, debris andmicroorganisms with the use of irrigants and medicaments. Thepractitioner in order to clean, debride, disinfect, and shape the pulpchamber needs to dislodge calcifications, remove pulpal tissue, removedebris, and eradcate microorganisms that are present. The dentalprofessional uses multiple medicaments and irrigants but none of theconventional irrigants or medicaments is able to eradicate Enterococcusfaecalis successfully as a single intra-canal medicament. Likewise, in abony cavity the soft tissue that needs to be removed is done with theintramedullary reaming which is similar to the removal of pulpal tissueby reaming during instrumentation.

Thus, there is a need for a composition and method that can moreeffectively and more efficiently dissolve tissues, remove debris, removethe smear layer, disinfect, eradicate microorganisms and dislodgecalcifications in the root canal treatment, for preparing surfaces forstem cell therapy, and for endodontic tissue regeneration. Further,there is also a need for a single intra-canal medicament that is abactericidal agent that eradicates Enterococcus faecalis withoutaffecting the micro hardness of dentin and which works within a shorttime.

SUMMARY OF THE INVENTION

The present invention addresses the needs presented above by providing,in its various embodiments, novel compositions that are capable oftissue dissolution, disinfection, tissue degradation, tissue removal,disruption of cellular function, and also effective methods of usingsuch compositions, as well as systems for treating patients which usethese compositions.

In one aspect, the present invention relates to a method of treating apatient that includes the irrigation of a bony cavity within a toothwith a thioglycolate-containing composition according to the inventionand the removal of pulpal tissue from the bony cavity. Irrigation of thecavity involves, in some cases, flowing the composition into the pulpalcavity (for instance, through a syringe and endodontic irrigation needleor curved syringe tip familiar to those skilled in the art) and removingit from the cavity. Alternatively or additionally, irrigation of thecavity is achieved by coating part of a medical instrument with thecomposition and then inserting the coated portion into the bony cavity.

The composition according to the invention containing thioglycolate usedin these methods can be adapted to disrupt disulfide bonds in softtissues and/or microbes (i.e. non-human microorganisms). When in use,the composition may contact a surface of the bony or pulpal cavity forvarious intervals, for example 30 seconds, 1 minute or 2 minutes more orless, etc., and may contact inner surfaces of the pulpal cavity thatinclude those most proximate to the root apex.

In various embodiments, the composition according to the inventionincludes a thioglycolate such as sodium or potassium thioglycolate,sodium hypochlorite, sodium chloride, oxygen, sodium chlorate, calciumhydroxide, and water, especially lime water and/or purified water,formulate so that the composition controls and eliminates tissues,affected by abnormal growth as in pulpitis, infected tissue, and ingranulomas. Hydroxides are typically present in various amounts insufficient concentrations within the composition to deprotonate thethioglycolate and/or a biomolecule in soft tissue.

The sodium hypochlorite present in the composition for tissuedissolution, disinfection, tissue degradation, tissue removal,disruption of cellular function according to the present inventionenhances the ability of the thioglycolate to disrupt disulfide bonds insoft tissues and/or in proteins present in various microbes in additionto its own tissue destroying action. Sodium hypochlorite requires over20 minutes to be antimicrobial however after 20 minutes, sodiumhypochlorite causes dental demineralization. The present inventionshortens the working time of sodium hypochlorite to under 20 minuteswhich is beneficial to preserving the mineral content of the dentin ofthe root. The composition is thus especially effective as a bactericidalagent because of the presence of both thioglycolate and hypochloriteworking together shorting the reaction time benefiting the patientstreatment.

The sodium chloride present in the composition interferes with membranepermeability, causes changes in a cell's metabolism, alters the cell'sability to function and changes the cell size by introducing osmoticstress to, facilitate debridement. The small amount of oxygen, in thecomposition can also react with cell membranes and disrupts the cellfunctions. Sodium chlorate is known as an antiseptic agent.

U.S. Pat. No. 8,808,718 discloses an antimicrobial composition forendodontic or periodontal treatments and surgery comprising inorganicacids, and/or salts thereof and optionally inorganic salts, such assodium chloride, but is silent regarding thioglycolic acid or its alkalimetal salts in particular. Both sodium chloride- and calciumhydroxide-containing compositions were tested against E. faecalis and P.aeruginsa for their effectiveness against these microorganisms. U.S.Pat. No. 8,808,718 does not disclose or suggest an antimicrobialcomposition for endodontic or periodontal treatments that containsreducing compounds, which attack the disulfide bonds in proteins foundin such microorganisms, such as potassium or sodium thioglycolate,together with alkali metal hypochlorite salts, but does teach thatsodium hypochlorite is a potent disinfectant for periodontal andendodontal applications, which attacks and destroys the organic matterof tissues. Thus the aforesaid U.S. Pat. No. 8,808,718 does not discloseor suggest the above-described the compositions for tissue dissolution,disinfection, tissue degradation, tissue removal, disruption of cellularfunction according to the present invention.

The present invention encompasses other methods as well. For instance,certain methods according to the invention involve irrigation of a bonycavity with a composition according to the invention that includes oneof the following reducing agents for breaking or disrupting disulfidebonds: potassium thioglycolate, calcium thioglycolate,2-mercaptoethanol, dithiothreitol, dithioerythritol,tris(2-carboxy-ethyl)phosphine, dithiobutylamine, and glutathione,together with sodium hypochlorite, sodium chloride, oxygen, sodiumchlorate, calcium hydroxide, and water, especially lime water and/orpurified water. Irrigation of the bony cavity (which may include, forexample, the pulpal cavity of a tooth, or a cavity generated or enlargedduring the operative removal of a carious lesion of the tooth) with thiscomposition degrades tissues and/or microbes (e.g. bacteria, viruses andfungi) within the bony cavity. As described above, irrigation of thecavity generally involves flowing the composition into the bony cavity(e.g. through a syringe and endodontic irrigation needle or syringe tip)and removing it from the cavity, or coating part of a medical instrumentwith the composition and then inserting the coated portion into the bonycavity. And, as above, the composition according to the invention maycontact a surface of the bony cavity for intervals that include, withoutlimitation, 30 seconds, 1 minute or more, 2 minutes or more or less. Thecomposition optionally contacts inner surfaces of the bony cavity thatinclude those most proximate to the root apex.

Other embodiments of the composition according to the invention fortissue dissolution, disinfection, tissue degradation, tissue removal,disruption of cellular function and antimicrobial action additionallycomprise a fragrance-imparting compound, lanolin, mineral oil urea,ceteryl alcohol and ceteareth-20.

In some embodiments the composition for tissue dissolution,disinfection, tissue degradation, tissue removal, disruption of cellularfunction is bactericidal and able to reduce the quantity of E. faecalisby 99% or more (e.g. 99.9%), so that in some cases, the composition canbe used as a restorative dental rinse to aid in, cleansing the surfaceof the dentin to aid in preventing recurrent infections.

Preferred embodiments of the antimicrobial composition for tissuedissolution, disinfection, tissue degradation and tissue removalaccording to the present invention contain from about 0 2% to about 6%sodium hypochlorite (NaOCl) by weight, from about 0.05% to about 2% ofpotassium thioglycolate by weight, and from, about 0.005 to about 8.0%,preferably about 0.008% of calcium hydroxide by weight. The solutionremains effective as long as there are negligible amounts of NaClO3. AspH is lowered below 11, significant amounts of NaOCl decompose to formNaCl, Na ClO₃ and small amounts of O₂ in the composition of theinvention which benefits the effectiveness of thiocoglycolate. Hence thecomposition according to the present invention is known to contain atleast some sodium chloride and sodium chlorate as well as small amountsof oxygen as well as the sodium hypochlorite when it is used.Furthermore the amounts of these products in the composition can vary inthe composition due to sodium hypo chlorite's rate of decomposition andpH while it sits prior to use. Higher concentrations of hypochloriteresult in faster decomposition so that a 15% solution decomposes 10×faster than a 5% solution. The decomposition rates increase withincreasing temperature.

During use in the methods according to the present invention thecomposition for tissue dissolution, disinfection, tissue degradation andtissue removal has a pH of about 5.5 to about 8. However when firstprepared a solution of about 6.5% sodium hypochlorite, about 0.01%Calcium hydroxide, and about 1% potassium thioglycolate in purifiedwater has a pH of about 8, but about 3 weeks later it had a pH of about6.5 and a taste similar to table salt.

Other methods encompassed by the invention include the steps of formingan access opening to expose a bony cavity within a tooth, irrigating thebony cavity that includes a reducing agent effective in disruptingdisulfide bonds in proteins, debriding the cavity and rinsing it toremove the composition, and filling the bony cavity with an inertfilling (e.g. gutta-percha and/or cement). The various embodiments ofthese methods can include the various optional features described above.

In another aspect, the present invention relates to methods of treatmentof inner surfaces of bony cavities more generally. Bony cavities mayexist in any osseous tissue including, without limitation, teeth, longbones, compact bone, spongy bone, and combinations thereof. Thesecavities may be naturally occurring (e.g., due to bone cysts) orman-made (e.g. voids left after resection of tumors or for implants).These methods generally involve contacting pulpal tissues and/ormicrobes within the bony cavity with a composition that includes, invarious embodiments, one or more of potassium thioglygolate, calciumthioglycolate, 2-mercapto ethanol, dithiothreitol, dithioerythritol,tris(2-carboxyethyl)phosphine, dithiobutylamine, and glutathione.Contacting materials (e.g. pulpal tissues, microbes and biofilms) withinthe bony cavity with the composition disinfects the bony cavity and/ordisrupts a tissue within the cavity.

In still another aspect, the present invention relates to a compositionfor dissolving tissues, disinfecting, deodorizing, degrading tissues,and removing tissue smear layer from a root canal treatment and within abony cavity. The novel composition of the present invention includescalcium hydroxide, sodium hydroxide, potassium thioglycolate, sodiumhypochlorite, sodium chloride, oxygen, sodium chlorate, water, mineraloil, urea, cetearyl alcohol, lanolin, aloe, fragrance, and ceteth-20,such that, the composition disrupts cellular functioning in at least oneof infected tissues, inflamed tissues, and pulpal tissues affected byabnormal growth, such as, in neoplasms.

The present invention further provides a novel composition of matterused for tissue dissolution, tissue degradation, disinfection,deodorize, lubricate, chelation, removal of tissue in a hard bonycavity, and preparing the hard bony cavity for placement of stem cellsand allow for tissue regeneration. The composition of matter Includescalcium hydroxide, sodium hydroxide, sodium hypochlorite, sodiumchlorate, sodium chloride, potassium thioglycolate, water, mineral oil,urea, cetearyl alcohol, and ceteth-20, such that, the novel compositionfor use within a bony cavity degrades pulpal, inflamed tissues, andtissues affected by abnormal growth in neoplasm and in infected tissueswith microorganisms.

Further, the present invention novel, use can provide a number ofadvantages, First, embodiments, of the present invention provide a novelcomposition and a novel method for using a chemical depilatory forendodontic usages. The present invention utilizes the ability of thechemical depilatory to break disulfide bonds in the tissues of pulpalarea. By breaking the disulfide bonds, the chemical depilatory providesfor weakening the structure of the pulpal tissue. Further, the presentinvention provides a composition that provides effective and quickresults as seen in apoptosis of bacteria in data from the experimentsperformed in the present invention. The chemical depilatories work at afast rate of within five minutes. The present invention's additionalcomponents function to decrease the thioglycolate's time needed to beeffective. In addition, the present invention is capable of functioningwithout causing dentin demineralizaton. The chemical depilatory'sability to be effective within minutes of its application provides anadvantage in patient care as patients can keep their mouth open for alimited time as the composition is applied to soft tissues of theinfected area. Further, tissues with granulomas are caused due toinfections. The present invention provides a novel depilatory havingapplications in dentistry and medicine. The present invention novel useof the depilatory's keratin-degrading has the ability to break thedisulfide bonds to interfere with a cell's ability to function, survive,and perpetuate in the pulpal tissue, infected tissue and tissue withabnormal growth. The present invention's novel use of breaking of thedisulfide bonds in the pulpal tissue, infected tissue, and tissue withabnormal growth that disrupts the cell's ability to survive causingapoptosis, and cell death in bacteria, yeast, and microorganisms. Thepresent invention additional components aid in disrupting the cell'sfunction which allows the chemical depilatory time needed to beeffective to be less.

Also, the present invention's depilatory is an intra-osseous irrigantthat is bactericidal for use against the microorganisms of Enterococcusfaecalis. Next, the present invention combines multiple applicationsinto a single medicament that can be used in the root canal treatmentson all types of tissue such as, but is not restricted to, abnormal,inflamed, normal and infected tissues. The present invention is achemical depilatory that breaks disulfide bonds by direct contactapplication on all types of tissues that have disulfide bonds that arein a bony cavity. As is well known to those of skill in the art,disulfide bonds are often critical to the proper folding and function ofproteins.

Further, regenerative endodontic utilizes irrigants, antimicrobialagents, and antibacterial agents on necrotic pulpal tissue fordisinfection and cleansing of the site so that regeneration occurs. Thepresent invention combines irrigants and antimicrobial agents into onecomposition for its use in endodontic regeneration for placement on thesite for regeneration. Further, the composition and the method arecapable of removing debris that is formed during dental procedure anddissolving proteins along with calcifications within the pulpal chamber.Furthermore, the present invention provides a composition that is alsocapable of bleaching teeth.

Further, the present invention novel use provides a method thatintegrates many processes to be effective at same time. The presentinvention novel use of a chemical depilatory in endodontic facilitatesthe removal of pulpal tissue and, bacteria and microorganisms. The noveluse of the chemical depilatory in endodontic facilitates removal ofcontents within the root canal treatment as it lubricates, irrigates,disinfects, dissolves, cleanses, deodorizes and removes the smear layer.Further the chemical depilatory has antimicrobial benefits. The noveluse of the present invention utilizes the chemical depilatory in asodium hypochlorite solution with additional components as a singleirrigant that combines tissue dissolving ability and smear layer removalcapacity with antibacterial properties. Further, the present inventionfacilitates breaking glycosaminoglycans (GAG) bond within the smearlayer and facilitates its removal. Also, the present invention novel useutilizing the chemical depilatory's ability to break disulfide bondspresent in proteins, Deoxyribonucleic acid (DNA), Ribonucleic acid(RNA), neoplastic and pulpal cells to further disrupts the ell's abilityto function. Further, the present invention, novel method and usedislodges pulpal calcification by breaking the bonds in the tissuesurrounding it. Next, the present invention novel method and usedissolves, removes and degrades tissues within the body that hasabnormal growth as in neoplasm as granulomas and/or infected tissuesthat includes bacteria, fungi (yeast), and microorganisms.

Further, the present invention in a novel method utilizes a chemicaldepilatory for removal of tissues from within a hard bony cavity. Thepresent invention utilizes the chemical depilatory in combination in asolution with sodium hypochlorite, sodium chloride and sodium chloratein the novel method and application and use for removing a soft tissue,necrotic tissue, debris, and calcified tissue from within the hardtissue cavity with having the ability to do so within 5 minutes.Further, the present invention provides a composition that is effectiveon unprepared tooth surfaces as well as on prepared tooth surfaces.Furthermore, the composition, provided by the present invention, isuseful in medicine, especially in long bones, in preparing skeletons formuseums etc. More generally, compositions and methods according tovarious embodiments of the invention are useful in any setting where theremoval of organic tissue and the sparing of bony tissue is desired.

These and other advantages will be apparent from the disclosure of thepresent invention contained herein.

The preceding is a simplified summary of the present invention toprovide an understanding of some aspects of the present invention. Thissummary is neither an extensive nor exhaustive overview of the presentinvention and its various embodiments. It is intended neither toidentify key or critical elements of the present invention nor todelineate the scope of the present invention but to present selectedconcepts of the present invention in a simplified form as anintroduction to the more detailed description presented below. As willbe appreciated, other embodiments of the present invention are possible,utilizing, alone or in combination, one or ore of the features set forthabove or described in detail below.

BRIEF DESCRIPTION OF THE DRAWINGS

The above and still further features and advantages of the presentinvention will become apparent upon consideration of the followingdetailed description of embodiments thereof, especially when taken inconjunction with the accompanying drawings, and wherein:

FIG. 1 is a cross sectional view of a tooth with tooth decay about to gounder treatment in accordance with an embodiment of the presentinvention;

FIG. 2 illustrates the tooth of FIG. 1 at a stage of treatment showingaccess to the pulpal chamber in accordance with an embodiment of thepresent invention;

FIG. 3 illustrates the tooth of FIG. 1 at a further stage of treatmentshowing a composition being applied in accordance with an embodiment ofthe present invention;

FIG. 4 illustrates the tooth of FIG. 1 at a further stage of treatmentshowing a composition accessing the cavity's floor in accordance with anembodiment of the present invention;

FIG. 5 illustrates the tooth of FIG. 1 at a further stage of treatmentshowing a rinsing solution in accordance with an embodiment of thepresent invention;

FIG. 6 illustrates the tooth of FIG. 1 at a further stage of treatment,showing the tooth after rinsing and the empty root canal, in accordancewith an embodiment of the present invention;

FIG. 7 is a flow chart depicting root canal treatment using acomposition, in accordance with an embodiment of the present invention;and

FIG. 8 illustrates structure of disulfide bonds in proteins according toan embodiment of the present invention.

The headings used herein are for organizational purposes only and arenot meant to be used to limit the scope of the description or theclaims. As used throughout this application, the word “may” is used in apermissive sense (i.e., meaning having the potential to), rather thanthe mandatory sense (i.e., meaning must). Similarly, the words“include,” “including,” and “includes” mean including but not limitedto. To facilitate understanding, like reference numerals have been used,where possible, to designate like elements common to the figures.

DETAILED DESCRIPTION

The present invention will be illustrated below in conjunction with anexemplary application, e.g., root canal treatment. Although well suitedfor use with, e.g., a medical application having disulfide bonds andrequiring breakage of disulfide bonds, the present invention is notlimited to any particular type of medical application. Those skilled inthe art will recognize the disclosed techniques may be used in anymedical or non-medical application in which it is desirable to providebreakage of disulfide bonds.

The phrases “at least one”, “one or more”, and “”and/or“” are open-endedexpressions that are both conjunctive and disjunctive in operation. Forexample, each of the expressions “at least one of A, B and C”, “at leastone of A, B, or C”, “one or more of A, B, and C”, “one or more of A, B,or C” and “A, B, and/or C” means A alone, B alone, C alone, A and Btogether, A and C together, B and C together, or A, B and C together.

The term “a” or “an” entity refers to one or more of that entity. Assuch, the terms “a” (or “an”), “one or more” and “at least one” can beused interchangeably herein. It is also to be noted the terms“comprising”, “including”, and “having” can be used interchangeably.

The term “automatic” and variations thereof, as used herein, refers toany process or operation done without material human input when theprocess or operation is performed. However, a process or operation canbe automatic, even though performance of the process or operation usesmaterial or immaterial human input, if the input is received beforeperformance of the process or operation. Human input is deemed to bematerial if such input influences how the process or operation will beperformed. Human input that consents to the performance of the processor operation is not deemed to be “material.”

The terms “determine”, “calculate” and “compute,” and variationsthereof, as used herein, are used interchangeably and include any typeof methodology, process, mathematical operation or technique.

In the following detailed description numerous specific details are setforth in order to provide a thorough understanding of embodiments orother, examples described herein. In some instances, well-known methods,procedures, compositions, or components have not been described indetail, so as to not obscure the following description. Further, theexamples disclosed are for exemplary purposes only and other examplesmay be employed in lieu of, or in combination with, the examplesdisclosed. It should also be noted the examples presented herein shouldnot be construed as limiting of the scope of embodiments of the presentinvention, as other equally effective examples are possible and likely.

FIG. 1 shows a cross-sectional view of a tooth 100 in accordance with anembodiment of the present invention. The tooth 100 includes tooth decay101, as shown in the figure. Because of the tooth decay 101, the tooth100 is under a treatment (i.e., root canal treatment). The tooth 100further includes enamel 102, a pulpal calcification 103, dentin 104, anda pulp 105. The tooth 100 further includes an apex 106 and a periodontalligament 107. The purpose of the root canal treatment is to completelyremove the pulp 105 (as it is infected or injured, and can infectsurrounding teeth), and that includes removal of all tissues, debris andmicroorganisms from root canal area.

Tissues of the pulp 105 differ from tissues of the enamel 102 andtissues of the dentin 104. Pulpal tissue is a highly vascular and softtissue. On other hand, the dentin 104 and the enamel 102 are hard,calcified, and mineralized tissues. The enamel 102 and the dentin 104include same type of inorganic materials, but differ in degree ofcalcification and mineralization of the inorganic material. Further,protein of the enamel 102 is resistant to enzymatic hydrolysis. Theenamel 102 is more resistant to enzymatic digestion than skin.Therefore, the protein of the enamel 102 is not classified as a type ofkeratin and is not affected by actions of a chemical depilatory, if thechemical depilatory is applied. Further, chemical composition of thetissues of the pulp 105 is different than chemical composition of thedentin 104 and the enamel 102.

According to an embodiment of the present invention, the pulp 105includes disulfide bonds. The disulfide bond is a covalent bond that isderived by coupling of two thiol groups. The linkage is called an SSbond or disulfide bridge. The disulfide bonds are present in a pluralityof living and non-living species. For example, disulfide bonds arepresent in bacteria as they serve as a protective role for bacteria.Further, in humans also, disulfide bonds are found in secretoryproteins, lysosomal proteins, and exoplasmic domains of stability ofproteins in, extracellular tissue. Further, disulfide bonds are alsofound in neuro-keratin of the myelinated sensory nerve A fibers.Furthermore, disulfide bonds are present in HNGB1 (high-mobility groupprotein-1), which is a mediator of inflammation. According to anembodiment of the present invention, a method is provided for utilizingthe disulfide Bond or S—S bond for cleaning out the pulp 105 andremoving tissue.

Tissues of the pulp 105 include disulfide bonds. Disulfide bonds actslike a glue and hold together molecules and proteins. If the disulfidebonds are broken, it may weaken and break down structure of the pulp 105and facilitate removal of tissues from the pulp 105.

FIG. 2 depicts the tooth 100, during the root canal treatment, accordingto an embodiment of the present invention. The pulpal chamber isaccessed, as shown in the figure. FIG. 2 further depicts access to thecavity 108, and access to cavity walls 109.

FIG. 3 depicts introduction of a composition 110 into the cavity 108,according to an embodiment of the present invention. The composition isplaced into the cavity 108 by using a disposable needle 111.

According to an embodiment of the present invention, the composition 110is a chemical depilatory. The present invention utilizes the chemicaldepilatory as an endodontic intra-canal medicament for irrigation,disinfection, and lubrication to provide antimicrobial properties andfurther facilitate removal of the smear layer. In an embodiment of thepresent invention, the composition 110 breaks the disulfide bonds in thepulpal tissue. The breakage of the disulfide bonds degrades structure ofthe pulpal tissue in order to remove tissue.

The chemical depilatories have been used for a wide variety of purposes.For example, chemical depilatories have been used for reducing microbiallevels on the hide of an animal. Further, the chemical depilatories havebeen used in removal of hair from skin and outer extremities as from thearms, legs, face, and underarms. Furthermore, the chemical depilatorieshave been used to remove unwanted hairs from the external skin of bothanimals and humans. However, chemical depilatories have never been usedin endodontics or in dentistry.

Further, tissues of the pulp 105 and hair have a similar characteristicof containing disulfide bonds as both are derived from neural crest stemcells. The hair follicle bulge is derived from cranial neural crest, andsimilarly the dental pulp and periodontal ligament are derived from theneural crest. Chemical depilatories has been used in hair removal onhumans and as an antimicrobial agent on hides of animals for yearssuccessfully, the present invention utilizes the chemical depilatoriesin a novel way for use in endodontic and for removal of tissue from abony cavity.

According to an embodiment of the present invention, the composition 110is composed of the following active ingredients: calcium hydroxide,sodium hydroxide, sodium hypochlorite and potassium thioglycolate. In anembodiment of the chemical depilatory composition of the presentinvention the composition 110 further includes mineral oil, urea,lanolin water, fragrance, cetearyl alcohol and ceteth-20 forcontributing to ability of the composition 110 to produce desiredresults.

According to an embodiment of the present invention, the composition 110is capable of dislodging calcifications that lie within root canalsystem by weakening attached connective tissue as well as removal ofsoft tissue from the cavity of a hard, bony tissue, In an embodiment ofthe present invention, the composition 110 provides a single endodonticirrigant composition that dissolves tissue, removes the smear layer, andincludes antibacterial capability.

Further, in an embodiment of the present invention, the composition 110(or chemical depilatory) may be used by a dental professional in anunprepared as well as prepared root canal system in order to facilitatethe instrumentation of root canal walls and pulpal chamber by dislodgingcalcificafions, removing pulpal tissue and debris.

The composition 110 may have multiple roles in the root canal treatment.For example, the composition 110 may act as an irrigant, disinfectant,conditioner, antimicrobial agent and lubricant for endodonticchemo-mechanical preparation of the root canal space, according to anembodiment of the present invention.

In various embodiments the composition 110 applied in the, methodsaccording to the present invention includes calcium hydroxide, sodiumhydroxide, and potassium thioglycolate, sodium hypochlorite, sodiumchloride, oxygen, and sodium chlorate in purified water. Further, in anembodiment of the present invention, the composition 110 may includemineral oil, urea, cetearyl alcohol and ceteth-20 for use forirrigation, disinfection, lubrication, removing the smear layer,dissolving pulpal tissue and as an anti-bacterial agent. In anembodiment of the present invention, the composition 110 may be in theform of, for example, but in not restricted to, a lotion, a cream, agel, a solution, and a paste. In another embodiment of the presentinvention, the composition 110 may be an emulsion, such as,micro-emulsion and macro-emulsion.

Further, in an embodiment of the present invention, lanolin as used asan emollient. Furthermore, in an embodiment of the present invention,water is used for diluting. Further, in an embodiment of the presentinvention, the composition 110 may also include aloe barbadensis as anemollient.

In an embodiment of the present invention, the composition 110 may beused in endodontic usages during intra-canal instrumentation in order tobreak disulfide bonds present in pulpal tissue, to remove the smearlayer, and to be effective against bacteria present in the root canalsystem. According to an embodiment, the composition 110 may be used as asingle endodontic irrigant on unprepared as well as prepared toothsurfaces in order to dissolve tissue, remove the smear layer, and beeffective against bacteria. The composition 110 may further provide forremoval of soft tissue inside of a hard, bony cavity. Further, accordingto an embodiment of the present invention, the composition 110 mayprovide preparation of regeneration and formation of mineralized andsoft tissue in a hard bony cavity (e.g., a human or animal).Furthermore, the composition 110 may be used as intraosseous irrigant,and in medicine, for example, in long bones and in preparing skeletonsfor museums etc.

FIG. 4 depicts the composition 110 accessing the cavity's floor 108 aswell as the cavity walls 109. The composition 110 provides removal ofsoft, connective tissue (i.e., pulp tissues) from within a hard tissuecavity (i.e., enamel and dentin) and hard bony cavities. In anembodiment of the present invention, the composition 110 is a chemicaldepilatory that removes soft tissue, necrotic tissue, debris, andcalcified tissue from within the hard tissue cavity. In an embodiment ofthe present invention, the composition 110 functions as an intra-canalmedicament with properties of an irrigant, disinfectant, lubricant,antimicrobial agent, debriding agent, and cleansing agent (as it iscapable of removing the smear layer). The composition 110 is furthercapable for chemo-mechanical cleansing and enlarging of the root canalsystem. Furthermore, the composition 110 is also capable of bleachingteeth.

According to an embodiment of the present invention, the composition 110includes the active ingredients of calcium hydroxide, sodium hydroxide,and potassium thioglycolate, sodium hypochlorite, sodium chloride,oxygen, and sodium chlorate in purified water, as discussed above.

In one, embodiment of the present invention, calcium hydroxide (presentin the composition 110) creates an alkaline environment so thatendodontic pathogens are not able to survive. Further, in an embodimentof the present invention, sodium hydroxide (which is a strong base) isused in tissue digestion by bleaching. Further, the sodium hydroxidebreaks down chemical bonds in tissue as bone remains present. The sodiumhypochlorite decomposes to sodium chloride, which interferes withmembrane permeability and functioning, and the antiseptic compoundsodium chlorate when the depilatory composition is at pH significantlyless than 11.

Further, in an embodiment of the present invention, potassiumthioglycolate (present in the composition 110) breaks down sulfur bondspresent in keratin protein of pulp. Potassium thioglycolate reacts withthe cystine present in the protein and can unfold various proteinswithin 30 seconds. The reaction is following: 2SH—CH2—COOH (thioglycolicacid)+R—S—S—R (cystine=disulfide bridge)--->2R—SH+COOH CH2 SS CH2 COOH(dithiodiglycolic acid).

Further, in an embodiment of the present invention the composition 110may include one or more of following constituents including, but notlimited to, water, mineral oil, urea, cetearyl alcohol, D&C yellow No.8, chromium hydroxide, theobroma cocoa seed butter, iron oxides,fragrances, and ceteareth-20. According to an embodiment of the presentinvention, the mineral oil may fill surface cracks. Those skilled in theart will appreciate that the surface cracks if not filled, may harborbacteria. Further, the mineral oil may act as a lubricant. Further,according to an embodiment of the present invention, the urea may retainmoisture and function as a keratolytic emollient.

Further, according to an, embodiment of the present invention, thecetearyl alcohol may include a coconut oil. The cetearyl alcohol canemulsify with ceterth-20 can to form cetereth-20 and enhances viscosityof the lotion.

Once, the pulp has been cleaned out and root canal area disinfected withhelp of the composition, a rinsing solution may be introduced, as shownin FIG. 5.

FIG. 5 shows introduction of a rinsing solution 112 using a disposableneedle 113 for applying the rinsing solution. FIG. 6 shows the tooth 100after rinsing with an empty root canal system 114.

According to an embodiment of the present invention, the composition 110(i.e., the chemical depilatory) breaks the disulfide bonds in the pulpaltissues. Therefore, any pulp stones attached to weakened pulpal tissuescan also be removed. The breaking of bonds aids in the removal ofunwanted pulpal tissue and debris. The composition 110 furtherlubricates, irrigates, disinfects, dissolves, cleanses and removes thesmear layer. Further, the composition 110 (or the chemical depilatory)provides antimicrobial protection against infections.

The composition 110 includes chemicals (that breaks the disulfide bonds,e.g., calcium hydroxide, sodium hydroxide, and potassium thioglycolate)with other substances (that are needed to lubricate, dissolve, disinfectand, remove pulpal debris, e.g., mineral oil, urea, cetearyl alcohol andceteth-20). The disulfide bonds are present in myelinated sheath ofnerves that enters the tooth via its apical opening. The composition 110weakens portion of the myelinated sheath of an entering nerve within theroot canal system, so that, it can be easily scraped off the inner rootcanal wall of the tooth. For example, the chemical depilatories removesthe hair from the follicle by weakening it at the point that it emergesfrom the follicle, the present invention utilizes the chemicaldepilatories in weakening nerve's protection by breaking down thedisulfide bond in the myelinated sheath that surrounds and protects thenerve.

Further, the composition 110 provides cleansing and debriding the pulpchamber and root canal space. The composition 110 further removes smearlayer by breaking the disulfide bonds present in glycosaminoglycans(GAG), which is the matrix of the inorganic layer Furthermore, thecomposition 110 provides dislodging pulpal calcifications by breakingbonds within the tissue that surrounds the calcification.

Hence, the composition 110 provides disinfecting, cleansing, irrigatingand lubricating both prepared and unprepared tooth surfaces duringdental procedures. The composition 110 may be used in endodontic duringnon-surgical root canal therapy during intra-canal chemo-mechanicalpreparation. Also, the composition 110 further may be used to remove thedebris that is formed during dental procedure and dissolve proteinswithin the pulpal chamber.

Further, according to embodiment of the present invention, thecomposition 110 may be used for cleaning, irrigating, disinfecting etc.of inside of any bony cavity (e.g., a hard bony cavity, a bony cavity incanines). For example, the composition may be used for intra-medullaryreaming and irrigating (e.g., to be used before a rod n orthopedics),maceration (e.g., cleaning animal skulls & bones used of preservingthem), preparing a bony surface for stem cells, for a site forregeneration of new tissue, and for removing tissue from inside a bonycavity to allow for the mineralized tissue.

Further, the composition 110 may be used for preparing a bony surfacefor cellular differentiation, tissue formation, and tissue regeneration.Those skilled in the art will appreciate that for making regeneration ofstem cells successful, the diseased or unwanted cells must be removed asthey damage the underlying tissues' ability to generate on its own newcells. In an embodiment of the present invention, the composition 110removes the diseased or unwanted, infected or inflamed cells, andprovides a clean area for regeneration of stem cells.

Further, the composition 110 may assist a dentist to prepare the toothsurface to place stem cells inside the tooth for pulpal and tissueregeneration. The stem cells may be used within the pulpal chamber. Forexample, an embodiment of the present invention provides a root, canaltherapy whereby a root canal procedure will be cleaning thechamber/roots and then placing stein cells to re-grow pulpal andmineralized tissue. Those skilled in the art will appreciate that thiscan only be performed if the composition 110 as described here in aboveis first used to clean the inside of the tooth 100, and failure to cleanthe inside of the tooth 100 sufficiently will not provide a clean enoughsurface for the placement of stem cells. The composition 110, providedby the present invention, provides cleaning of the inside of the tooth100 and provides a clean surface for placement of stem cells.Furthermore, according to an embodiment of the present invention, thecomposition 110 may also provide bleaching of teeth as it removes thedead blood which is dark in color from within the teeth that gives thetooth a dark shade.

FIG. 7 is a flowchart of a method 700 for cleaning out pulp anddisinfecting root canal area in a root canal treatment, according to anembodiment of the present invention. According to an embodiment of thepresent invention, the method 700 provides using a chemical depilatoryas a composition in endodontic. The method 700 is effective due todisulfide bonds presence in pulpal tissue.

At step 702, a chemical depilatory composition is dispensed intodisposal tubes. Further, disposal needles may be attached to thedisposable tubes. According to an embodiment of the present invention,the composition may include sodium chlorate, sodium hydroxide, andpotassium thioglycolate. In one embodiment of the present invention,calcium hydroxide (present in the composition) creates an alkalineenvironment so that endodontic pathogens are not able to survive.Further, in an embodiment of the present invention, sodium hydroxide(which is a strong base) is used in tissue digestion. Further, sodiumchlorate is an antiseptic agent. Further, the sodium hydroxide breaksdown chemical bonds and further keeps bones intact. Furthermore, in anembodiment of the present invention, potassium thioglycolate (present inthe composition) breaks down sulfur bonds present in protein of pulp,tissue. In another embodiment of the present invention, potassiumthioglycolate is a thiol-based depilatory.

In another embodiment of the present invention, the composition mayfurther include mineral oil, oxygen, sodium chloride, sodiumhypochlorite, urea, cetearyl alcohol, D&C yellow No. 8, chromiumhydroxide, theobroma cocoa seed butter, iron oxides, fragrances andceteareth-20 to enhance its functioning, in addition to calciumhydroxide, sodium hydroxide, sodium hypochlorite and potassiumthioglycolate. According to an embodiment of the present invention, themineral oil may act as a lubricant. Further, according to an embodimentof the present invention, the urea may retain moisture, preventinfections, treat inflammatory conditions, and function as a keratolyticemollient. Further, according to an embodiment of the present invention,the cetearyl alcohol can emulsify with ceterth-20 can to formcetereth-20 and enhances viscosity of the lotion, In an embodiment, thecetearyl alcohol may include a coconut oil. Furthermore, in anembodiment of the present invention, the fragrance acts as deodorizers.

At step 704, a few drops of the composition are placed in a pulpalchamber to wet the floor with the disposable needle. At step 706, thecomposition or solution is placed it at opening of the canal for goinginside the canal with help of an endodontic file/reamer/instrument ofchoice, coat the ‘file’ with the solution and. In an embodiment of thepresent invention, the opening of the canal may include, but is notrestricted to, soft tissues. The solution is left there for about 1-3minutes.

At step 708, the composition or solution is rinsed with warm water.Further, in an embodiment of the present invention, the solution mayalso be rinsed with warm sodium hypochlorite. In another embodiment ofthe present invention, the solution may also be rinsed with othercommercial, conventional irrigants. Further, the pulp and pulpal debrisis removed and irrigated out.

At step 710, it is determined whether the pulpal calcifications orinfected/damaged area of tooth has been completely removed anddislodged, and the canal area has been completely disinfected. In case,there are still some tissues of pulp remaining or infection remaining,flow of the method 700 returns to the step 702. Otherwise, the method700 proceeds towards step 712, wherein the pulpal canal is prepared forobturation. In an embodiment of the present invention, a mechanicalinstrument procedure may be carried out for obturating the pulpal canaland then the method 700 concludes.

FIG. 8 illustrates disulfide bonds in proteins according to anembodiment of the present invention. Disulfide bonds 802 present intissue proteins of a human body may be considered as a framework forliving cell. In an embodiment of the present invention, in a human body,let say, are infected area having neoplastic cells is present in tissue.By using the present invention the infected area of the human body maybe treated by a chemical depilatory that can cause apoptosis in abnormalcells. The present invention applied to the infected area breaksdisulfide bonds 802 present. When the disulfide bonds 802 are broken inthe infected tissue, a doctor may prevent regeneration of the neoplasticcells in that area. Further, DNA, RNA or proteins are dependent upon thedisulfide bonds 802 for their integrity and existence. Therefore, oncethe disulfide bonds 802 are broken, the cell loses its ability forfunctioning and regeneration. Cellular breakdown results in theprevention and arrest of abnormally growing cells.

The foregoing disclosure has focused on exemplary depilatorycompositions which disrupt disulfide bonds. These exemplary compositionsare not intended to be limiting, however, and it should be appreciatedthat any composition or active pharmaceutical ingredient whicheffectively reduces such disulfide bonds can fall within the scope ofthe various systems and methods of the invention. Exemplary activeingredients suitable for use in the various embodiments of the inventioninclude, without limitation, potassium thioglygolate, calciumthioglycolate, 2-mercaptoethanol, dithiotheitol, dithioerythritol,tris(2-carboxyethyl)phosphine, dithiobutylamine, and glutathione, aswell as combinations of two or more of these ingredients.

The various methods of the present invention generally involve theapplication of the compositions described above to contact materials inbony cavities such as the pulpal cavity of a tooth. These compositionsare applied, in some cases, by irrigating the bony cavities withflowable compositions that can be delivered through syringes andirrigation needles or flexible tips familiar to those of skill in theart. In other cases, the compositions are pastes that are placed in bonycavities using a spatula and/or by coating an instrument such as anendodontic file with the paste and then using the instrument tomechanically debride the bony cavity. As the examples below demonstrate,the compositions can contact various surfaces within the cavity forintervals normally associated with endodontic irrigation and de-pulping,such as 1, 5, 15 or 30 minutes.

Compositions of the invention are delivered in any suitable format foruse in an endodontic or general dental office. In one group ofembodiments, a composition is provided in a pre-filled syringe which isoptionally packaged with one or more irrigation needles or flexible tipsand/or directions for use that set out one of the methods for irrigatinga bony cavity discussed above.

Although the foregoing disclosure has focused on examples in theendodontic setting, compositions according to various embodiments of theinvention are useful in a variety of other settings. While not wishingto be bound by any theory, in general, compositions of the invention donot degrade “bony” tissues comprising hydroxyapatite (which lacksdisulfide bonds), such as tooth or bone. However, non-bony tissues(“soft” tissues) and microbes are generally much more susceptible todisruption. Accordingly, in one group of preferred embodiments,compositions of the invention are disposed within body cavities whichare at least partially defined by bony tissues (“bony cavities”). Bonycavities can be naturally occurring, such as the marrow cavity of a boneor the pulpal cavity of a tooth. Alternatively or additionally, bonycavities can be at least partially man made, for instance in the courseof operative removal of a carious lesion from a tooth, or due to theresection of tumorous tissue from a bone. With respect to operativetreatment for carious lesions in particular, it is believed that methodsof the invention advantageously permit the disinfection of bony cavitiesbefore they are filled, thus reducing the risk of recurrence of thelesion or of other undesirable sequelae. As the following examplesdemonstrate, compositions of the invention are, advantageously,effective in, reducing titers of streptococcus mutans, which is known tocontribute to the formation of carious lesions in teeth.

Compositions of the present invention are also useful for disinfectingbony cavities and surfaces for taxidermy or pathology purposes. Incertain embodiments, for instance, a composition of the invention isapplied to bony cavities in cadaver skeletons to prepare them fordisplay.

Test Results

Test results will now be provided here to illustrate the aboveprinciples. The following example illustrates working of the presentinvention in accordance with an embodiment of the present invention. Aperson of ordinary skill in the art will appreciate the presentinvention may be performed for any medical use and is not limited to anyparticular medical application.

Testing of the composition according to the present invention'santi-microbial activity was done in an independent laboratory inaccordance with the USFDA Regulations 21 CFR Part 58. The testing of thepresent invention was done under the supervision of a quality assurancesupervisor and a study director. The study was done at an off-sitelaboratory that performed the tests under protocol that includesreproducibility of test results and details to allow for inspection. Thelaboratory keeps all the documentation and details on file.

Preferred embodiments of the antimicrobial composition for tissuedissolution, disinfection, tissue degradation and tissue removalaccording to the present invention are composed of the following activeingredients: from, about 0.2% to about 6% sodium hypochlorite (NaOCl),from about 0.5% to 2% of potassium thioglycolate, and about 0.0001 to8.0% calcium hydroxide in purified water. All the foregoing percentagesare by weight.

Test results for the antimicrobial effectiveness of a single exemplarycomposition according to the invention are reported herein below,although several other exemplary compositions were prepared and tested.The exemplary composition was prepared by mixing about 5.6% sodiumhypochlorite, about 1% of potassium thioglycolate, and about 0.01%calcium hydroxide into purified water. The initial pH of this mixturewas 7.97, but after three weeks (when the antimicrobial effectivenesswas measured) the pH had reached about 6.5. The exemplary compositioncan be readily used for endodontic applications at these pH values.

However sodium hypochlorite reacts with water at these pHs to formhypochlorous acid, which is unstable and decomposes. Sodium hypochloritedecomposes according to the following two reactions (a) and (b) to formNaCl, NaClO₃ and oxygen:

3NaOCl≈2NaCl+NaClO₃   (a)

2NaOCl≈2NaCl+O₂   (b).

As a result of the reactions a and b and approximate known decompositionpathway ratios (a/b is about 9/1), the following chemical species werepresent in the antimicrobial exemplary composition in the followingrespective theoretically calculated amounts after three weeks (the timeinterval between the preparation of the exemplary composition and thetests).

Calculated Amounts of Chemical Species in the Tested AntimicrobialComposition at the Time of the Testing

Test Solution 1:

Sodium hypochlorite (NaOCl) 0.3859% Potassium thioglycolate 1.0120%Calcium hydroxide (Ca(OH)₂) 0.0080% Sodium Chloride (NaCl) 2.8400%Oxygen 0.1100% Sodium chlorate (NaClO₃) 2.2200% Purified water 93.4180%*All amounts of chemical species are in weight percent

Test Solution 2: NaOCl: 5.24% CaOH: 0.0128%

Potassium thioglycolate: 2.02%

Purified Water: 92.72% Test Solution 3: NaOCl: 278% CaOH: 0.008%Potassium Thioglycoclate: 1.01% Purified Water: 96.20%

The testing of the test organisms was performed with respective contacttimes of 30 seconds, 1 minutes and 2 minutes after introducing theaforesaid exemplary antimicrobial composition. The time intervals werechosen so as to correspond to times that practitioners use in clinicalpractice. The maximum time was chosen as 2 minutes, since actualtreatment time should be below 10 minutes to prevent unwanted dentinaldemineralization. Keeping patient's mouth open for 30 minutes maximumfor a procedure is reasonable which would allow for amble time fortreatment in a tooth with multiple canals. Recovery times were testedfor bacteria using 2-5 days times since they are the same for otherorganisms as C. albicans with 2-5 days in. Recovery values are thecolonies forming abilities. The testing took place a bout three weeks,after preparation of the exemplary antimicrobial composition.

The plate counts are based on colony formation units (CFU)/plate for E.facailis bacteria. For bacteria, the 25-250 CPU/plate are statisticallyaccurate range. Soybean Casein Digest Agar was used as the medium forplates of the test organism of E. faecalis. All plates were handledunder laboratory conditions with their controls.

The test microorganism was E. faecalis because they are the prevalentorganisms in Endodontic infections. Endodontic infections are mixedmicroorganisms or flora. However, Enterococci faecalis are themicroorganisms that have a major presence in the endodontic lesion,which all need to be eradicated. E. faecalis is the organism that hasbeen indicated as the most persistent and prevalent organisms found inendodontic cases that become reinfected. Other microorganisms as Candidaalbicans and Streptococcus mutan can be eliminated from the root canalsystem but E. faecalis is the organism that is known to persist.Furthermore, S. mutans has a significant presence in root canalinfections as, it is known as the organism producing tooth decay, sinceit has the ability to, survive levels of oxygen tension and absence ofessential nutrients. S. mutans can maintain microbial growth andcontinue acid production at low pH values. S. mutans and Candidaalbicans can be eliminated in root canal therapy while E. Faecalis andis resistant. Enterococcus faecalis, bacteria, is found most commonly inpersistent radiographic lesions after root canal treatment. Due to theprevalence of E. faecalis in persistent endodontic infections, it isessential that the main persistent etiologic agent is eradicated duringroot canal instrumentation. Therefore, complete removal of irritantsfrom the root anal system is best and most effective way to eradicateroot canal infections.

The test procedure for evaluation of products (the antimicrobialcomposition) for anti-microbial activity against selected organisms atrepresentative contact times is described herein below. Products wereevaluated in a liquid matrix. The test organisms and contact times werechosen. This is a quantitative test that allows the determination of theamount of organism reduction at pre-determined intervals. All testmethod acceptance criteria were met, The acceptance criteria were thatnegative controls should be negative for growth, positive controlsshould be positive for growth, and neutralization should be confirmed atabout 70%. Specific criteria for pass/fail of the test article weredetermined.

Inoculum Preparation: Plates of Soybean Casein Digest Agar (SCDA) mediawere inoculated with stock cultures of the test organisms E. faecalisand incubated at 30-35° C. for 18-48 hours. Plates of Sabouraud DextroseAgar (SDEX) media were inocul ted with stock cultures of the testorganism C. Growth was harvested from the surface using a sterile bentglass rod and Physiological Saline Solution 0.9%(DHSS).

Where necessary, culture suspensions were adjusted for the testprocedure with PHSS to approximately (about) 10⁸ CFU/ml using visualturbidity.

Test Article Preparation: Test articles were prepared according to theproduct label or sponsor instructions and were tested without anyadditional manipulation or dilution.

Neutralization: A 0.1 ml aliquot of the test article was mixed with 9.9ml Dey-Engley Neutralizer Broth (DEYE). An additional tube of 10 mL ofDEYE was prepared as a titer control. The tubes were inoculated with 0.1ml of a test organism suspension diluted to approximately <10000 thenmixed thoroughly. Aliquots from each tube were plated in triplicate ontoSCCA and incubated at 30-35 C.° for 2-5 days for E. faecalis.

Controls: Positive control tubes containing 10 mL PHSS were prepared. A0.1 mL aliquot of the test organism was added to each tube. The positivecontrol was assayed at 0 hour and the longest tested time point. Thenegative control consisted of plating sterile aliquots of applicableliquid media in triplicate and incubating as described in the testprocedure.

Test Procedure: Tubes containing 10 mL of each test article wereprepared and inoculated with 0.1 mL of the test organism to yield 10⁶CFU/mL. The test articles were mixed thoroughly.

At 30 seconds, 1 minutes and 2 minutes of exposure, 1.0 mL aliquots ofthe test suspension were removed and added to 9 mL of neutralizer andserially diluted to produce a 1:100 dilution of test suspension toneutralizer. The tubes were mixed thoroughly. Serial dilutions were madein the appropriate neutralizer and assayed using a standard spread platemethod.

All plating was performed in triplicate. Bacterial test articles wereplated onto SCDA and incubated at 30-35° C. for 2-5 days.

Quantitative analysis was used to study the anti-microbial activity ofthe present invention. The following formulas were used by theindependent laboratory in preparing their report of the effectiveness ofthe present invention.

Calculations: The log reduction values were calculated using thefollowing formula: log reduction=log₁₀U−log₁₀ C

wherein, U=Average positive control titer, C=Average recovered counts

The percent reduction values were calculated using the followingformula: % Reduction=[1−1/10^(log reduction))]×100

The percent neutralization is obtained according to the followingequation: % Neutralization=[(Average Sample Count/Plate)/(AverageControl Count/Plate)]×100

The Results:

TABLE I Test Article 1 - Enterococcus faecalis Average Average TestExposure Control titer Article Titer Percent Identification Intervals(CFU/ml) (CFU/ml) Reduction Log₁₀ Reduction Control 2 min 2.4 × 10(7) 1.7 × 10⁷ ≈28 ≈0.14 — 30 sec. — <2.0 × 10² >99.99916 >5.08 Sample 1 min1.1 × 10⁷ <2.0 × 10² >99.99916 >5.08 I 2 min — <2.0 × 10² >99.99916>5.08

TABLE II Test Solution 2: Average Average Test Exposure Control titerArticle Titer Percent Identification Intervals (CFU/ml) (CFU/ml)Reduction Log₁₀ Reduction Control 2 min 2.4 × 10⁷  1.7 × 10 (7) 28 0.14— 30 sec. — <2.0 × 10² >99.9916 >5.08 Sample 1 min 2.4 × 10⁷ <2.0 ×10² >99.9916 >5.08 2 2 min — <2.0 × 10² >99.9916 >5.08

TABLE III TEST SOLUTION 3: SAMPLE 3: 30 sec & 1 min & 2 min <2.0 × 10(2) >99.9916 >5.08

TABLE IV Neutralization of Organism E. facaelis: Average Control AverageTest Percent ORGANISM Counts (CFU) Article Counts (CFU) NeutralizationTest Solution 1 39 35 111 Test Sotution 2 36 35 103 Test Solution 3 3035 86

The qualitative analysis, given here, confirms that the presentinvention is very useful and successful in its ability to disinfect thepulpal chamber from the test microorganism E. faecalis. The qualitativeanalysis for all of the three test solutions at all of the timeintervals had a greater than 99.99916% reduction of test microorganism.Neutralization of the microorganisms was successful because all of thepercentage for neutralization was over 70% which was needed forconfirmation. Furthermore, in the recovery testing, there were coloniesforming units in any of the plates with any of the test microorganisms.Therefore, the microorganisms did not regenerate and did not reappear.The lack of the microorganisms present in the recovery results provesthat the present invention is able to eradicate all the testmaterials/microorganisms during the instrumentation.

The above test results demonstrate that the composition, as provided bythe present invention, provides anti-microbial activity against aboveorganism E. faecalis which is the most resistant organism in recurrentendodontic retreatments. E. faecalis is more persistent and difficult toeradicate than C. albicans, and S. mutans. Further, the tests show thatthe present invention, composition, or chemical depilatory providesunexpected results proving its useful in endodontic usages foreradicating E. faecalis and other microorganisms as C. albicans and S.mutans in a very short time. Furthermore, the test results prove thatthe present invention is able to prevent E. faecalis from recovering.Therefore, these test results prove that the present invention is novelin its use and have the ability to eradicate microorganisms inendodontic therapies. Further, the test results prove that the presentinvention is a novel single intra-canal medicament and as an effectivebactericidal agent that kills E. faecalis.

The present invention may be useful to eradicate the microorganisms fromother bony cavities having infections due to one of the microbes or amicroorganisms like E. faecalis. If a bacteremia resulted after a dentalprocedure, these microbes y appear in other bony cavities or onorthopedic prosthesis that may benefit from the present invention'sbactericidal ability. In canines, their bony cavities in the middle andinner ear can be Infected by bacteria (Streptococcus) and/or fungi(Candida). Both of these microorganisms can be killed by the presentinfection.

Further, the test results prove that the present invention wassuccessful in utilizing the chemical depilatory's ability to breakdisulfide bonds in bacteria and yeast to disrupt the functioning of theinfected cells with the microbes. Therefore, disrupting the ability ofthe bacteria, yeast, and infected cells to function causes the cells todegrade facilitating the removal of tissues. Further, the test resultsprove that the present invention is able to disrupt the disulfide bondsin living cells and tissues.

Unless explicitly stated otherwise all amounts of chemical compounds andother materials are expressed in % by weight, based on the total amountof material present.

The exemplary systems and methods of this present, invention have beendescribed in relation to a root canal treatment and removal of tissuefrom within a hard bony structure. However, to avoid unnecessarilyobscuring the present invention, the preceding description omits anumber of known structures and devices. This omission is not to beconstrued as a limitation of the scope of the claimed invention.Specific details are set forth to provide an understanding of thepresent invention. It should however be appreciated that the presentinvention may be practiced in a variety of ways beyond the specificdetail set forth herein.

Also, while the flowcharts have been discussed and illustrated inrelation to a particular sequence of events, it should be appreciatedthat changes, additions, and omissions to this sequence can occurwithout materially affecting the operation of the present invention.

A number of variations and modifications of the present invention can beused. It would be possible to provide for some features of the presentinvention without providing others.

While the foregoing is directed to embodiments of the present invention,other and further embodiments of the present invention may be devisedwithout departing from the basic scope thereof. It is understood thatvarious embodiments described herein may be utilized in combination withany other embodiment described, without departing from the scopecontained herein. Further, the foregoing description is not intended tobe exhaustive or to limit the present invention to the precise formdisclosed, Modifications and variations are possible in light of theabove teachings or may be acquired from practice of the presentinvention.

Certain exemplary embodiments may be identified by use of an open-endedlist that includes wording to indicate the list items are representativeof the embodiments and the list is not intended to represent a closedlist exclusive of further embodiments. Such wording may include “e.g.,”“etc.,” “such as,” “for example,” “and so forth,” “and the like,” etc.,and other wording as will be apparent from the surrounding context.

No element, act, or instruction used in the description of the presentapplication should be construed as critical or essential to the presentinvention unless explicitly described as such, Also, as used herein, thearticle “a” is intended to include one or more items, Where only oneitem is intended, the term “one” or similar language is used. Further,the terms “any of” followed by a listing of a plurality of items and/ora plurality of categories of items, as used herein, are intended toinclude “any of,” “any combination of,” “any multiple of,” and/or “anycombination of” multiples of the items and/or the categories of items,individually or in conjunction with other items and/or other categoriesof items.

The present invention, in various embodiments, configurations, andaspects, includes components, methods, processes, systems and/orapparatus substantially as depicted and described herein, includingvarious embodiments, sub-combinations, and subsets thereof. Those ofskill in the art will understand how to make and use the presentinvention after understanding the present disclosure. The presentinvention, in various embodiments, configurations, and aspects, includesproviding devices and processes in the absence of items not depictedand/or described herein or in various embodiments, configurations, oraspects hereof, including in the absence of such items as may have beenused in previous devices or processes, e.g., for improving performance,achieving ease and/or reducing cost of implementation.

The foregoing discussion of the present invention has been presented forpurposes of illustration and description. The foregoing is not intendedto limit the present invention to the form or forms disclosed herein. Inthe foregoing Detailed Description for example, various features of thepresent invention are grouped together in one or more embodiments,configurations, or aspects for the purpose of streamlining thedisclosure. The features of the embodiments, configurations, or aspectsof the present invention may be combined in alternate embodiments,configurations, or aspects other than those discussed above. This methodof disclosure is not to be interpreted as reflecting an intention thatthe claimed invention requires more features than are expressly recitedin each claim. Rather, as the following claims reflect, inventiveaspects lie in less than all features of a single foregoing disclosedembodiment, configuration, or aspect. Thus, the following claims arehereby incorporated into this Detailed Description, with each claimstanding on its own as a separate preferred embodiment of the presentinvention.

Moreover, though the description of the present invention has includeddescription of one or more embodiments, configurations, or aspects andcertain variations and modifications, other variations, combinations andmodifications are within the scope of the present invention, e.g., asmay be within the skill and knowledge of those in the art, afterunderstanding the present disclosure. It is intended to obtain rightswhich include alternative embodiments configurations, or aspects to theextent permitted, including alternate, interchangeable and/or equivalentstructures, functions, ranges or steps to those claimed, whether or notsuch alternate, interchangeable and/or equivalent structures, functions,ranges or steps are disclosed herein, and without intending to publiclydedicate any patentable subject matter.

What is claimed is:
 1. A method of treating a patient, which comprisesthe steps of: (a) irrigating a pulpal cavity of a tooth with acomposition, said composition comprising a thioglycolate, sodiumhypochlorite, sodium chloride, oxygen, sodium chlorate, calciumhydroxide, and purified water; and (b) removing pulpal tissue from thepulpal cavity.
 2. The method according to claim 1, wherein the step ofirrigating the pulpal cavity includes flowing the composition into thepulpal cavity.
 3. The method according, to claim 2, further comprisingthe step of providing a syringe having a barrel at least partiallyfilled with the composition, wherein flowing the composition into thepulpal cavity includes expelling the composition from the syringethrough an endodontic irrigation needle or syringe tip into the pulpalcavity.
 4. The method according to claim 1, wherein the step ofirrigating the pulpal cavity includes coating a portion of a medicalinstrument with the composition and inserting the coated portion intothe pulpal cavity.
 5. The method according to claim 1, wherein thecomposition is adapted to disrupt a disulfide bond in at least one ofthe pulpal tissue and a microbe.
 6. The method according to claim 1,wherein irrigating the pulpal cavity comprises degrading the pulpaltissue, thereby facilitating the step of removing the pulpal tissue fromthe pulpal cavity.
 7. The method according to claim 1, wherein thecomposition further comprises at least one additional compound selectedfrom the group consisting of sodium hydroxide, fragrance, lanolin,mineral oil urea, ceteryl alcohol and ceteareth-20.
 6. The methodaccording to claim 7, wherein the hydroxide is present in thecomposition in an amount effective to deprotonate at least one of thethioglycolate and a biomolecule present in a soft tissue.
 9. The methodaccording, to claim 1, wherein said composition is made by mixingpotassium thioglycolate, sodium hypochlorite and calcium hydroxide withwater to form an aqueous mixture and wherein, at least initially onformation, said aqueous mixture contains from about 0.2% to about 6% byweight of sodium hypochlorite, from about 0.05% to about 2% by weight ofpotassium thioglycolate, and about 0.010 to about 0.005% by weight ofcalcium hydroxide.
 10. A method of treating a patient having a bony,cavity, said method comprising the step of: irrigating the bony cavitywith a composition comprising a reducing compound, sodium hypochloriteand water, wherein said reducing compound is selected from the groupconsisting of potassium thioglycolate, calcium thioglycolate,2-mercaptoethanol, dithiothreitol, dithioerythritol,tris(2-carboxyethyl)phosphine, dithiobutylamine and glutathione; therebydegrading at least one of a soft tissue and a microbe within the bonycavity.
 11. The method according to claim 10, wherein the bony cavityincludes a pulpal cavity of a tooth and the soft tissue includes apulpal tissue.
 12. The method according to claim 10, further comprisingthe step of removing from the bony cavity at least one of a tissue and abacteria that has been degraded.
 13. The method according to claim 10,wherein the step of irrigating the bony cavity includes flowing thecomposition into the bony cavity.
 14. The method according to claim 13,further comprising the step of providing a syringe having a barrel atleast partially filled with the composition, wherein flowing thecomposition into the bony cavity includes expelling the composition fromthe syringe through an endodontic irrigation needle or syringe tip intothe bony cavity.
 15. The method according to claim 10, wherein the stepof irrigating the bony cavity includes coating a portion of a medicalinstrument with the composition and inserting the coated portion intothe bony cavity.
 16. The method according to claim 10, wherein the stepof irrigating a bony cavity includes degrading at least one of a softtissue and a microbe by contacting one or more of a prepared surface, anunprepared surface, and a biofilm.
 17. The method according to claim 10,wherein the step of irrigating a bony cavity includes contacting anabnormally growing tissue, thereby degrading it.
 18. The methodaccording to claim 10, wherein the composition further comprises atleast one additional ingredient selected from the group consisting of acalcium hydroxide, sodium hydroxide, sodium chlorate, sodiumhypochlorite, sodium chloride, oxygen, fragrance-imparting compounds,lanolin, mineral oil, urea, ceteryl alcohol and ceteareth-20.
 19. Themethod according to claim 10, wherein the bony cavity is formed by theoperative treatment of a carious lesion in a tooth.
 20. The methodaccording to claim 19, wherein the composition is a restorative rinse.21. The method according to claim 19, wherein the composition iseffective to reduce a quantity of E. facaelis within the bony cavity byat about 99%.
 22. A method of treating a patient, said method comprisingthe steps of: (a) forming an opening for accessing a bony cavity withina tooth; (b) irrigating the bony cavity with a composition comprising areducing agent effective in disrupting disulfide bonds in proteins;debriding the bony cavity; and rinsing the bony cavity, thereby removingthe composition therefrom; wherein said reducing agent is selected fromthe group consisting of potassium thioglycolate, calcium thioglycolate,2-mercaptoethanol, dithiothreitol, dithioerythritol,tris(2-carboxyethyl)phosphine, dithiobutylarnine and glutathione; andwherein said composition comprises of one or more of the said reducingagent, sodium hypochlorite, sodium chloride, oxygen, sodium chlorate,calcium hydroxide, oxygen, and purified water.
 23. The method accordingto claim 22, wherein the step of irrigating the bony cavity includesflowing the composition into the bony cavity.
 24. The method accordingto claim 23, further comprising the step of providing a syringe having abarrel at least partially filled with the composition, wherein flowingthe composition into the bony cavity includes expelling the compositionfrom the syringe through an endodontic irrigation needle or syringe tipinto the bony cavity.
 25. The method according to claim 22, wherein thestep of irrigating the bony cavity includes coating a portion of amedical instrument with the composition and inserting the coated portioninto the bony cavity.
 26. The method according to claim 22, wherein thestep of irrigating a bony cavity includes contacting a pulpal tissue ora microbe with the composition.
 27. The method according to claim 22,wherein the reducing agent is a thioglycolate and the compositionincludes an hydroxide, fragrance, lanolin, mineral coil, urea, ceterylalcohol and ceteareth-20.
 28. The method according to claim 22, whereinthe step of irrigating the bony cavity includes contacting a surface ofa pulp tissue or a biofilm within the bony cavity with the compositionfor 5 minutes or more.
 29. The method according to clam 22, wherein thebony cavity is formed by the operative treatment of a carious lesion ina tooth.
 30. The method according to claim 22, wherein said reducingagent is said potassium thioglycolate, and wherein said composition ismade by mixing potassium thioglycolate, sodium hypochlorite and calciumhydroxide into purified water to form an aqueous mixture and wherein, atleast initially on formation, said aqueous mixture contains from about0.2% to about 6% by weight of sodium hypochlorite, from about 0.05% toabout 2% by weight of potassium thioglycolate, and about 0.01 to about0.005% by weight of calcium hydroxide.